Lamin A involvement in ageing processes

•Lamin A is a main constituent of the nuclear lamina: mutations in LMNA gene and altered post-translational maturation of prelamin A may cause accelerated ageing of tissues and progeroid syndromes.•Several ageing-related processes are affected by lamin A: mTOR signaling, epigenetic regulation and chromatin dynamics, microRNA expression, mechanosignaling, stress response and inflammation.•Lamin A may serve as a sensor of cell intrinsic and environmental conditions, regulating cellular response through transient increase of prelamin A levels.•In cells that accumulate prelamin A forms due to impaired processing, a permanent stress response condition is set out, which accelerates ageing-related processes. Lamin A, a main constituent of the nuclear lamina, is the major splicing product of the LMNA gene, which also encodes lamin C, lamin A delta 10 and lamin C2. Involvement of lamin A in the ageing process became clear after the discovery that a group of progeroid syndromes, currently referred to as progeroid laminopathies, are caused by mutations in LMNA gene. Progeroid laminopathies include Hutchinson-Gilford Progeria, Mandibuloacral Dysplasia, Atypical Progeria and atypical-Werner syndrome, disabling and life-threatening diseases with accelerated ageing, bone resorption, lipodystrophy, skin abnormalities and cardiovascular disorders. Defects in lamin A post-translational maturation occur in progeroid syndromes and accumulated prelamin A affects ageing-related processes, such as mTOR signaling, epigenetic modifications, stress response, inflammation, microRNA activation and mechanosignaling. In this review, we briefly describe the role of these pathways in physiological ageing and go in deep into lamin A-dependent mechanisms that accelerate the ageing process. Finally, we propose that lamin A acts as a sensor of cell intrinsic and environmental stress through transient prelamin A accumulation, which triggers stress response mechanisms. Exacerbation of lamin A sensor activity due to stably elevated prelamin A levels contributes to the onset of a permanent stress response condition, which triggers accelerated ageing.